Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD

Zhu, Jie; Mallia, Patrick; Footitt, Joseph; Qiu, Yusheng; Message, Simon D.; Kebadze, Tatiana; Aniscenko, Julia.; Barnes, Peter.J.; Adcock, Ian M.; Kon, Onn M.; Johnson, Malcolm; Contoli, Marco; Stanciu, Luminita A.; Papi, Alberto; Jeffery, Peter K.; Johnston, Sebastian L.

Abstract Background Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity. Objectives To determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16-induced COPD exacerbations and its relationship to disease severity. Methods Bronchial mucosal inflammatory cell phenotypes were determined at pre-infection baseline and following experimental RV infection in 17 GOLD stage II COPD subjects and as controls, 20 smokers and 11 non-smokers, with normal lung function. No subject had a history of asthma/allergic rhinitis: all were negative for aero-allergen skin prick tests. Results RV-infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T-lymphocytes in COPD and non-smokers. Monocytes/macrophages, CD4+ T- and CD20+ B-lymphocytes were increased in all subjects. At baseline, compared to non-smokers, COPD subjects and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T-lymphocytes but fewer numbers of CD4+ T- and CD20+ B-lymphocytes. The virus-induced inflammatory cells in COPD were positively associated with virus load, illness severity and reductions in lung function. Conclusion Experimental rhinovirus infection induces bronchial mucosal eosinophilia and neutrophilia only in COPD and monocytes/macrophages and lymphocytes in both COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load, illness severity. Anti-viral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations.